Browsing 500 Presentations
PAEDIATRICS MENINGITIS SURVEILLANCE IN CÔTE D’IVOIRE AND USE OF IB-VPD/PBM TO MONITOR PCV IMPACT (ID 201)
- Cho n'din catherine Boni, Côte d'Ivoire
- Alice Britoh, Côte d'Ivoire
- Flore Zaba, Côte d'Ivoire
- Lepri Aka, Côte d'Ivoire
- Rebecca Kouamé, Côte d'Ivoire
- Hamidou Koné, Côte d'Ivoire
- Koffi Nzué, Côte d'Ivoire
- Rowan Bancroft, Côte d'Ivoire
- Jason M. M. Mwenda, Congo
- Brenda Kwambana, Côte d'Ivoire
- Antonio Martin, Côte d'Ivoire
Abstract
Background
National paediatric bacterial meningitis (PBM) surveillance began in 2002 in Côte d’Ivoire. This surveillance is under the supervision of the immunization program. The aim of this work was to describe the PBM surveillance in Côte d’Ivoire and use of IB-VPD/PBM to monitor PCV impact.
Methods
The paediatric service notifies suspected cases, collect and send the CSF samples to the laboratory. The laboratory receives and analyse CSF and do the management of data. The technical, logistical and financial support were provided by WHO, CDC and Regional Laboratory of GAMBIA MRC. The national immunization program provided feedback to central level.
Results
From January 2002 to December 2019, 7769 CSF samples were submitted to the sentinel site laboratory. Of these samples, 263(3.39%) gave a positive culture with bacterial growth. S. pneumoniae, 50.57% (133 /263) H. influenzae 30.08 (87 /263) and 5.7 % (15/263) N. meningitidies over all the years of monitoring. Pneumococcal conjugate vaccine (PCV) serotypes, 5, 18C, 19F and 6A/B were identified post-vaccine introduction.
Conclusions
This surveillance generated data used for to evidence of disease burden, and advocacy to introduce in routine immunization Pneumococcal conjugate vaccine -13 (PCV 13) in 2014.
A NOVEL VACCINE (GAMMA-PN) THAT INDUCES SEROTYPE INDEPENDENT IMMUNITY TO STREPTOCOCCUS PNEUMONIAE (ID 203)
INTERCHANGEABILITY OF PHID-CV10 AND PCV13 IN PRIMARY COURSE SCHEDULES (ID 204)
- Amanda J. Leach, Australia
- Nicole Wilson, Australia
- Jemima Beissbarth, Australia
- Kim E. Mulholland, Australia
- Mathuram Santosham, United States of America
- Peter McIntyre, Australia
- Paul V. Licciardi, Australia
- Mark Chatfiled, Australia
- Victor Oguoma, Australia
- Jonathan Carapetis, Australia
- Sue Skull, Australia
- Heidi Smith-Vaughan, Australia
- Vicki Krause, Australia
- Ross Andrews, Australia
- Peter Morris, Australia
- Paul Torzillo, Australia
Abstract
Background
In remote communities of northern Australia, we previously demonstrated that the onset of otitis media (OM) in Aboriginal infants was preceded by acquisition of bacterial pathogens that colonise the nasopharynx (NP) soon after birth. We aimed to determine safety and effectiveness of mixed vaccine schedules against early infection due to non-typeable Haemophilus influenzae and Streptococcus pneumoniae.
Methods
In an open-label controlled trial, we randomised (1:1:1) Aboriginal infants at 28 to 38 days of age, to either Prevenar13™ (P, PCV13) at 2-4-6 months of age (_PPP), Synflorix™ (S, PHiD-CV10) at 2-4-6 months (_SSS), or Synflorix at 1-2-4 months plus Prevenar13 at 6 months (SSSP). Primary outcomes (assessor-blinded) were immunogenicity at 7 months of age against pneumococcal serotypes 3, 6A, and 19A, and protein D (GMCs and proportions of infants with IgG > 0·35 µg/mL or > 100 EL.U/mL, respectively). Secondary immunogenicity outcomes at 2 and 4 months are also reported.
Results
A 4-dose early 1-2-4-6 month combination schedule of Synflorix plus Prevenar13 (SSSP) provided superior overall immune protection against serotypes 3, 6A, 19A, and protein D, compared to standard 3-dose 2-4-6 month schedules (_SSS or _PPP).
Conclusions
These vaccines can be combined safely and effectively within this primary schedule, with no evidence of immune suppression.
PNEUMOCOCCAL SEROTYPE 6B REQUIRES KDM6B, A HISTONE DEMETHYLASE, FOR ASYMPTOMATIC INFECTION (ID 205)
Abstract
Background
Streptococcus pneumoniae is a natural colonizer of the human respiratory tract, and a global priority pathogen comprised of over 90 different serotypes. Respiratory epithelial cells are among the first to encounter the organism, however, their role in orchestrating the response to infection is unknown.
Methods
We compared epithelial cell responses to serotype 4 (Tigr4), causing lethal symptomatic infection in mice, to a serotype 6B, which induces asymptomatic infection even at high inoculum.
Results
We found these interactions lead to divergent responses in either asymptomatic, host-limiting infection, or symptomatic, invasive pneumococcal infection. Our data show that 6B induces a distinct inflammatory profile in comparison to Tigr4, which requires KDM6B, a eukaryotic histone demethylase, and the cytokine IL-11. At the molecular level, we reveal that KDM6B demethylation of histone H3 remodels the promoter of IL-11 for expression. Finally, through chemical inhibition of KDM6B enzymatic activity, or exogenous addition of IL-11, the asymptomatic and symptomatic host response to pneumococcus can be interchanged.
Conclusions
Thus, we show for the first time that asymptomatic infection is driving a host response dependent on KDM6B and IL-11, and these factors are critical in modulating a divergent response to different pneumococcal serotypes.
IN VIVO DUAL RNA-SEQ ANALYSIS REVEALS THE BASIS FOR DIFFERENTIAL TISSUE TROPISM OF CLINICAL ISOLATES OF STREPTOCOCCUS PNEUMONIAE (ID 208)
Abstract
Background
Recently we showed that a single nucleotide polymorphism (SNP) in the raffinose pathway regulatory gene rafR accounts for differences in the capacity of clonally-related pneumococcal strains to cause localised versus systemic infection. However, the underlying mechanism for these differences remain unclear.
Methods
6h post intranasal infection, a time-point were the wildtype and rafR-swapped strains are present in the lungs at similar levels, RNA was isolated from murine lungs. Host and pathogen transcriptomes were then simulatenously sequenced.
Results
The Dual RNA-seq data highlighted that this SNP extensively impacts both bacterial and host transcriptomes in infected lungs, affecting bacterial carbohydrate utilization and host inflammatory responses. A crucial role was predicted for differential neutrophil recruitment in the distinct virulence profiles of the infecting strains. Single cell analysis revealed that reduced expression of the RafR regulon, driven by the single rafR SNP, leads to massive recruitment of neutrophils and bacterial clearance in the lungs. Importantly, the observed disease outcomes were confirmed by in vivo neutrophil depletion showing that early detection of bacteria by the host in the lung environment is crucial for effective clearance.
Conclusions
Dual RNA-seq provides a powerful tool for understanding complex host-pathogen interactions, revealing how a single pneumococcal SNP drives differential disease outcomes.
PHOSPHORYLATION OF GALR IS CRITICAL FOR GALACTOSE METABOLISM IN STREPTOCOCCUS PNEUMONIAE (ID 209)
INTEGRATION OF PERCH DATA INTO CLINEPIDB, AN OPEN-SOURCE CLINICAL EPIDEMIOLOGY DATABASE RESOURCE (ID 210)
- Sheena Tomko, United States of America
- Cristina Aurrecoechea, United States of America
- John Brestelli, United States of America
- Brian Brunk, United States of America
- Danielle Callan, United States of America
- Dave Falke, United States of America
- Steve Fischer, United States of America
- Danica Helb, United States of America
- Jay Humphrey, United States of America
- John Judkins, United States of America
- Jessica Kissinger, United States of America
- Brianna Lindsay, United States of America
- David Roos, United States of America
- Christian Stoeckert, United States of America
- Jie Zheng, United States of America
Abstract
Background
Population-based epidemiological studies provide opportunities for innovation and collaboration among global-health researchers. ClinEpiDB (https://clinepidb.org) is an open-access online resource that enables investigators to maximize the utility and reach of their research and make optimal use of data from others.
Methods
ClinEpiDB was built on EuPathDB infrastructure - a collection of databases covering eukaryotic pathogens, related species, and hosts. Data is integrated via a unified semantic web framework. An intuitive web interface overlays SQL queries with results visualized via interactive applications in the ClinEpiDB browser, providing insight into data distributions and covariate associations.
Results
ClinEpiDB, first released in 2018, contains datasets from the MAL-ED and GEMS enteric disease projects, SCORE schistosomiasis project, and ICEMR malaria studies. Integration of the Pneumonia Etiology Research for Child Health (PERCH) study, with ~1000 variables for >9500 children from 9 sites, will provide a rich source of information for the pneumonia research community. Once public (expected 2020-2021), investigators will be able to explore all PERCH data through the ClinEpiDB browser before deciding whether to request download access.
Conclusions
The ClinEpiDB resource provides an intuitive interface to view data and will continue to grow with integration of new datasets, enhanced tool development, and user outreach and education.
IMPACT OF BINDING RESPIRATORY SYNCYTIAL VIRUS ON PNEUMOCOCCAL CELL DIVISION AND ANTIBIOTIC SENSITIVITY (ID 214)
Abstract
Background
There is increasing evidence that severe pneumococcal disease is associated with coinfection with respiratory syncytial virus (RSV). Our previous work demonstrated a direct interaction between these pathogens, with RSV glycoprotein (RSV-G) binding penicillin binding protein (PBP) 1a of S. pneumoniae. This interaction led to enhanced virulence in a murine pneumonia model. This study aimed to determine the mechanism behind this, by examining the direct effects of RSV-G on PBP1a activity and bacterial division.
Methods
Clinical pneumococcal strains were screened for their ability to bind a purified recombinant RSV-G using immunoblot assays, fluorescence and electron microscopy. The effect on PBP1a activity was determined using enzymatic assays and by testing antibiotic susceptibility.
Results
Using fluorescent amino acid pulse labelling we observed RSV-G binding to the site of active pneumococcal cell wall synthesis. Following RSV-G exposure, pneumococci had morphological defects and increased lysis compared to controls, but growth rate was not reduced. PBP1a glycosyltransferase activity was not inhibited by RSV-G, while some pneumococci exhibited enhanced penicillin sensitivity.
Conclusions
RSV-G results in increased pneumococcal cell wall abnormalities and cell lysis. This may enhance pneumococcal virulence through the increased release of pneumolysin toxin. The implicated role of PBPs in RSV-G binding may be relevant to beta-lactam antibiotic usage.
RESOLVING THE PERSISTENCE OF SEROTYPE 19A IN IRELAND AFTER PCV13 INTRODUCTION, RESULTS FROM 2007-2018 (ID 219)
COST-EFFECTIVENESS OF PCV13 IN IMMUNOCOMPETENT US ADULTS AGED 65 YEARS: IMPORTANCE OF VACCINE EFFECTIVENESS AGAINST SEROTYPE 3 (ID 220)
Abstract
Background
Accumulating—albeit limited—evidence indicates that PCV13 is effective against serotype 3 (ST3), which causes a disproportionate share of pneumococcal disease in US adults. Estimates of protection employed in economic evaluations have varied widely; we thus examined the importance of vaccine effectiveness (VE) against ST3 in determining the cost-effectiveness of PCV13.
Methods
A probabilistic cohort model depicting risks and costs of pneumococcal disease was employed to evaluate the cost per QALY gained with PCV13->PPSV23 versus PPSV23 alone in immunocompetent US adults aged 65 years under alternative assumptions regarding VE-PCV13 versus ST3. VE-PCV13 (excl. ST3) was based on data from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA); VE-PPSV23 against IPD was based on published literature, and against CAP, was zero.
Results
Cost per QALY gained with PCV13->PPSV23 (vs. PPSV23) ranged from $449,304 to $184,807 when varying VE-PCV13 versus ST3 from 0% to 125% of point-estimates from published literature.
Conclusions
Cost-effectiveness of PCV13 in immunocompetent US adults aged 65 years varies considerably under alternative assumptions regarding VE-PCV13 versus ST3. When assuming a reasonable value for VE-PCV13 versus ST3, results suggest that PCV13 provides acceptable value for money in this patient population.
IMPACT OF 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE (PCV13) ON NON-BACTEREMIC PNEUMOCOCCAL PNEUMONIA (NBPP) IN THE UNITED STATES 2013-2017 (ID 222)
- Ryan Gierke, United States of America
- Almea Matanock,
- Nong Shang,
- Monica Farley, United States of America
- William Schaffner, United States of America
- Ann Thomas, United States of America
- Arthur Reingold, United States of America
- Lee Harrison, United States of America
- Katherine Schleiss,
- Kari Burzlaff, United States of America
- Susan Petit, United States of America
- Nisha Alden,
- Tamara Pilishvili, United States of America
Abstract
Background
PCV13 was recommended for U.S. children in 2010 and for adults ≥65 years in 2014. Vaccine coverage among adults ≥65 years was 43% in 2017. We evaluated PCV13 impact on NBPP among adults.
Methods
NBPP cases (clinically or radiographically-confirmed pneumonia and a positive pneumococcal urine antigen test in a hospitalized adult aged ≥18 years) were identified at select hospitals in 10 sites within CDC’s Active Bacterial Core surveillance during 2013-2017. NBPP rates (cases per 100,000) were estimated using U.S. Census Bureau population denominators and adjusted for the proportion of pneumonia patients tested by UAT and the number of pneumonia admissions in the catchment area.
Results
Between 2013 and 2017, 4,430 NBPP cases were identified. From 2013 to 2014, rates of NBPP declined from 153 to 90 (41% reduction, 95%CI 30%, 51%) in ≥65 year-olds; 60 to 40 (34% reduction, 95%CI 22%, 45%) in 50-64 year-olds; and 15 to 10 (36% reduction, 95%CI 25%, 47%) in 18-49 year-olds. From 2014 to 2017, rates of NBPP increased in all ages but remained below 2013 rates (Figure).
Conclusions
Reductions in NBPP among adults were primarily due to indirect effects of PCV13 use in children, with no additional declines following PCV13 introduction for adults aged ≥65 years.